The overall objectives of this project are to understand the endocrinology of the human glycoprotein hormones, thyroid-stimulating hormone (TSH), choriogonadotropin(hCG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH), and thereby to develop diagnostic and therapeutic clinical applications. Recent research advances in the current period include the following: Development of a new diagnostic test, the nocturnal TSH surge test, for diagnosis of central hypothyroidism in children and demonstration of its superiority to the standard thyrotropin-releasing hormone test; elucidation of the structure of the oligosaccharide moieties of the beta-core molecule of pregnancy; delineation of the fundamental kinetic parameters governing beta-core metabolism in human subjects; determination of the beta-core levels in pregnancy serum and in postmenopausal urine; and demonstration of the primary nephrogenous origin of beta-core in normal pregnancy. Future directions of the project will include the following: Investigation of structure-function relationships of the glycoprotein hormones using molecular biological techniques such as site-directed mutagenesis; characterization of the natural evolution of the heterogeneity of oligosaccharide structures of hCG and its subunits throughout pregnancy; and assessment of the roles of defects in the nocturnal TSH surge and subtle abnormalities of pituitary-thyroid axis function as causes of short stature and delayed growth in childhood.